Evaluation of anti-Candida potential of geranium oil constituents against clinical isolates of Candida albicans differentially sensitive to fluconazole: inhibition of growth, dimorphism and sensitization

Abstract

Fluconazole (FLC) susceptibility of isolates of Candida spp., (n = 42) and efficacy as well as mechanism of anti-Candida activity of three constituents of geranium oil is evaluated in this study. No fluconazole resistance was observed among the clinical isolates tested, however 22% were susceptible-dose-dependent (S-DD) [minimal inhibitory concentration (MIC) ≥ 16 μg ml(-1)] and a standard strain of C. albicans ATCC 10231 was resistant (≥ 64 μg ml(-1)). Geraniol and geranyl acetate were equally effective, fungicidal at 0.064% v/v concentrations i.e. MICs (561 μg ml(-1) and 584 μg ml(-1) respectively) and killed 99.9% inoculum within 15 and 30 min of exposures respectively. Citronellol was least effective and fungistatic. C. albicans dimorphism (Y → H) was highly sensitive to geranium oil constituents tested (IC50 approximately 0.008% v/v). Geraniol, geranyl acetate and citronellol brought down MICs of FLC by 16-, 32- and 64-fold respectively in a FLC-resistant strain. Citronellol and geraniol arrested cells in G1 phase while geranyl acetate in G2-M phase of cell cycle at MIC(50). In vitro cytotoxicity study revealed that geraniol, geranyl acetate and citronellol were non-toxic to HeLa cells at MICs of the C. albicans growth. Our results indicate that two of the three geranium oil constituents tested exhibit excellent anti-Candida activity and significant synergistic activity with fluconazole.